It is generally known that the therapeutic action of a medicine in a living organism depends greatly upon the carrier by which the medicine is administered. High demands are made upon the pharmaceutical preparation, especially for drugs which are taken orally.
The first requirement is high bioavailability; that is, as much active substance as possible should be made available to the organism In the treatment of infections with an antibiotic-containing composition, which is the object of this invention, optimal blood levels of the antibiotic should be reached in the shortest possible time.
The second requirement is that the dosage form should be free from administration problems However, the dosage form with the best bioavailability is seldom easy to use and, conversely, one which is easily taken often does not have a satisfactory bioavailability.
Tablets are pharmaceutical formulations with several advantages. Tablets are easy to use with respect to dosing, storing, transporting and administering. However, many patients experience difficulties when swallowing a tablet and, moreover, the absorption of the active substance may be contingent on the dissolution rate of the tablet.
An aqueous solution or dispersion of the drug is easily ingested, is better absorbed by the patient and gives high initial blood concentrations However, a liquid is cumbersome to dose and to transport Moreover, it should often be prepared shortly before delivery to the patient, and stored at a low temperature. Sometimes preserving agents should be added to such a liquid preparation.
Therefore, so-called disperse tablets have been developed which, when immersed in water, rapidly disintegrate to provide a suspension of the drug, thus combining certain advantages of both dry and liquid dosage forms. Tablets of this type are described in European patent application EP-A-181650, German patent DE 1617343 and in J. Pharm. Pharmac. (1976), 28, 234-238. These known disperse tablets are not fully satisfactory, however, especially when directly ingested, because these tablets disintegrate already in the mouth into a pappy mass which is unpleasant to swallow. For some kinds of drugs, such as beta-lactam antibiotics improved types of disperse tablets have been developed, as described in European patent application EP-A-0281200.
Tetracyclines, especially doxycycline, are frequently prescribed medicines. However, no process is known for the preparation of tetracycline containing tablets which can either be easily swallowed, or quickly provide a fine dispersion when immersed in water.